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Sex-and bone-specific responses in bone structure to exogenous leptin and leptin receptor antagonism in the ovine fetus

Sex-and bone-specific responses in bone structure to exogenous leptin and leptin receptor antagonism in the ovine fetus
Sex-and bone-specific responses in bone structure to exogenous leptin and leptin receptor antagonism in the ovine fetus

Widespread expression of leptin and its receptor in developing cartilage and bone suggests that leptin may regulate bone growth and development in the fetus. Using microcomputed tomography, this study investigated the effects of exogenous leptin and leptin receptor antagonism on aspects of bone structure in the sheep fetus during late gestation. From 125 to 130 days of gestation (term ~145 days), chronically catheterized singleton sheep fetuses were infused intravenously for 5 days with either saline (0.9% saline, n = 13), recombinant ovine leptin at two doses (0.6 mg·kg-1·day-1 LEP1, n = 10 or 1.4 mg·kg-1·day-1 LEP2, n = 7), or recombinant superactive ovine leptin receptor antagonist (4.6 mg·kg-1·day-1 SOLA, n = 6). No significant differences in plasma insulin-like growth factor-I, osteocalcin, calcium, inorganic phosphate, or alkaline phosphatase were observed between treatment groups. Total femur midshaft diameter and metatarsal lumen diameter were narrower in male fetuses treated with exogenous leptin. In a fixed length of femur midshaft, total and bone volumes were reduced by the higher dose of leptin; nonbone space volume was lower in both groups of leptin-treated fetuses. Leptin infusion caused increments in femur porosity and connectivity density, and vertebral trabecular thickness. Leptin receptor antagonism decreased trabecular spacing and increased trabecular number, degree of anisotrophy, and connectivity density in the lumbar vertebrae. The increase in vertebral porosity observed following leptin receptor antagonism was greater in the malecompared with female, fetuses. Therefore, leptin may have a role in the growth and development of the fetal skeleton, dependent on the concentration of leptin, sex of the fetus, and bone type examined.

Femur, Metatarsal, Vertebra
0363-6119
R781-R790
De Blasio, Miles J.
7f76249e-a431-4da4-ad18-089136d68b07
Lanham, Stuart A.
28fdbbef-e3b6-4fdf-bd0f-4968eeb614d6
Blache, Dominique
733e6794-0388-42c1-b8a6-031782a26aa1
Oreffo, Richard O.C.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Fowden, Abigail L.
78847bb7-4d2d-4e79-93c8-a90e0131c1d6
Forhead, Alison J.
8ad02d28-a814-4b74-93ff-9c29a254019c
De Blasio, Miles J.
7f76249e-a431-4da4-ad18-089136d68b07
Lanham, Stuart A.
28fdbbef-e3b6-4fdf-bd0f-4968eeb614d6
Blache, Dominique
733e6794-0388-42c1-b8a6-031782a26aa1
Oreffo, Richard O.C.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Fowden, Abigail L.
78847bb7-4d2d-4e79-93c8-a90e0131c1d6
Forhead, Alison J.
8ad02d28-a814-4b74-93ff-9c29a254019c

De Blasio, Miles J., Lanham, Stuart A., Blache, Dominique, Oreffo, Richard O.C., Fowden, Abigail L. and Forhead, Alison J. (2018) Sex-and bone-specific responses in bone structure to exogenous leptin and leptin receptor antagonism in the ovine fetus. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 314 (6), R781-R790. (doi:10.1152/ajpregu.00351.2017).

Record type: Article

Abstract

Widespread expression of leptin and its receptor in developing cartilage and bone suggests that leptin may regulate bone growth and development in the fetus. Using microcomputed tomography, this study investigated the effects of exogenous leptin and leptin receptor antagonism on aspects of bone structure in the sheep fetus during late gestation. From 125 to 130 days of gestation (term ~145 days), chronically catheterized singleton sheep fetuses were infused intravenously for 5 days with either saline (0.9% saline, n = 13), recombinant ovine leptin at two doses (0.6 mg·kg-1·day-1 LEP1, n = 10 or 1.4 mg·kg-1·day-1 LEP2, n = 7), or recombinant superactive ovine leptin receptor antagonist (4.6 mg·kg-1·day-1 SOLA, n = 6). No significant differences in plasma insulin-like growth factor-I, osteocalcin, calcium, inorganic phosphate, or alkaline phosphatase were observed between treatment groups. Total femur midshaft diameter and metatarsal lumen diameter were narrower in male fetuses treated with exogenous leptin. In a fixed length of femur midshaft, total and bone volumes were reduced by the higher dose of leptin; nonbone space volume was lower in both groups of leptin-treated fetuses. Leptin infusion caused increments in femur porosity and connectivity density, and vertebral trabecular thickness. Leptin receptor antagonism decreased trabecular spacing and increased trabecular number, degree of anisotrophy, and connectivity density in the lumbar vertebrae. The increase in vertebral porosity observed following leptin receptor antagonism was greater in the malecompared with female, fetuses. Therefore, leptin may have a role in the growth and development of the fetal skeleton, dependent on the concentration of leptin, sex of the fetus, and bone type examined.

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ajpregu.00351.2017 - Accepted Manuscript
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Accepted/In Press date: 7 February 2018
e-pub ahead of print date: 4 June 2018
Published date: June 2018
Keywords: Femur, Metatarsal, Vertebra

Identifiers

Local EPrints ID: 422477
URI: http://eprints.soton.ac.uk/id/eprint/422477
ISSN: 0363-6119
PURE UUID: 7640c285-b1d0-4623-82df-c1ad2bc53266
ORCID for Stuart A. Lanham: ORCID iD orcid.org/0000-0002-4516-264X
ORCID for Richard O.C. Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

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Date deposited: 24 Jul 2018 16:30
Last modified: 26 Nov 2021 07:19

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Contributors

Author: Miles J. De Blasio
Author: Stuart A. Lanham ORCID iD
Author: Dominique Blache
Author: Abigail L. Fowden
Author: Alison J. Forhead

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